Citrin缺陷导致的新生儿肝内胆汁淤积症家系SLC25A13基因突变研究  

SLC25AI3 gene mutation analysis in a pedigree of neonatal intrahepatic cholestasis caused by citrin deficiency

作　　者：宋元宗[1] 牛饲美晴[2] 盛建胜[2] 饭岛干雄 小林圭子[2] 

机构地区：[1]暨南大学附属第一医院儿科,广州510630 [2]鹿儿岛大学医齿学终合研究科分子病熊生化学教研室

出　　处：《中华儿科杂志》2007年第6期408-412,共5页Chinese Journal of Pediatrics

基　　金：日本学术振兴会亚非科学平台项目(JSPS AA Science Platform Program:学振地第330号);日中医学协会助成金(日中医発第117号);中国国家重点基础研究发展计划(2001CB510305);中国广东省科技计划(2004B50301018)

摘　　要：目的探讨一个来自中国的 Citrin 缺陷导致的新生儿肝内胆汁淤积症(NICCD,MIM#605814)家系的基因诊断过程。方法从先证者及其所在家系其他9名成员的血样中提取 DNA,PCR扩增后行琼脂糖凝胶电泳,初步发现2个突变,并用本实验室建立的基因扫描法进一步证实,然后行DNA 测序,最终确定突变位置和性质。结果先证者为851-854del 和1638-1660dup 两种突变的复合杂合子,两种突变分别位于 SLC25A13基因外显子9和外显子16。母亲及哥哥为851-854del 携带者,父亲、一个姑姑及其子为1638-1660dup 携带者。结论该家系中 SLC25A13基因外显子9和16分别发生了缺失突变851-854del 和插入突变 1638-1660dup。Objective Neonatal intrahepatic cholestasis caused by citrin deficiency （ NICCD, MIM #605814） is an inherited metabolic disease resulting from mutations of the gene SLC25A13, which encodes citrin, a liver-type mitachondrial aspartate-glutamate carrier. Mutation analysis is necessary for definitive diagnosis of NICCD patients. So far （ March, 2007）, 36 kinds of mutation, including 7 nonsense, 10 missense, 11 abnormal splicing, 4 insertion and 4 deletion, have been identified by Kobayashi＇ s group, who cloned the gene in Kagoshima, Japan. To date, most of the NICCD patients reported in the world are Japanese. This study aimed to explore the gene diagnosis procedure of two known SLC25A13 mutations in a pedigree with an NICCD patient from China. Methods DNA was extracted from dried blood spots collected with filter papers from the proband and other 9 members in a NICCD pedigree from China, and then PCR amplification and agarose gel electrophoresis were performed, revealing two mutations preliminarily, which were further proved by Genescan, a procedure established in our laboratory already. Furthermore, the positions and characteristics of the mutations were finally confirmed by DNA sequencing. Results The proband is a compound heterozygote of two mutations, 851-854del in exon 9 and 1638-1660dup in exon 16 of SLC25A13 gene. His mother and brother carry the former mutation, which predicts a frameshift and introduction of a stop codon at position 286, while his father, one aunt and her son carry the latter, resulting in a frameshift at codon 554, and introducing a stop codon at position 570. Conclusion A deletion mutation 851-854del in exon 9 and an insertion mutation 1638-1660dup in exon 16 of SLC25A13 gene were identified in the pedigree, providing reliable evidences for both diagnostic confirmation of the patient and the genetic counseling from other members in the pedigree.

关 键 词：线粒体蛋白质类 膜转运蛋白质类 突变 钙结合蛋白质类 有机阴离子转运子 胆汁淤积 肝内 

分 类 号：R722.1[医药卫生—儿科]